Photolytic artificial lung

ABSTRACT

The present invention is directed to a photolytic artificial lung. The photolytic artificial lung converts water to oxygen for blood absorption, regulates pH, the removes carbon dioxide, and co-produces electrical power is disclosed. The photolytic artificial lung includes a photolytic cell where all of the chemical reactions occur. The photolytic cell disclosed herein can also be used to direct chemical reactions in organs other than the lung. Also disclosed herein is a gas sorption device for removing carbon dioxide from the system by chemical sorption.

FIELD OF THE INVENTION

This application is a divisional application of U.S. Patent ApplicationSer. No. 09/920,385, filed Aug. 1, 2001, now U.S. Pat. No. 6,866,755 B2,which is incorporated herein by reference in its entirety.

The present invention is directed to a photolytic artificial lung thatutilizes light energy to achieve physiological gas exchange in fluids,such as in the blood stream of a patient experiencing respiratorydifficulties, and to a photolytic cell used for the same. It findsparticular applications in conjunction in the field of artificial organsand the medical arts. However, it is to be appreciated, that theinvention will also find applications in related fields due to thephoto-electro chemical transformations involved therein.

BACKGROUND OF THE INVENTION

The lung is the main organ in the respiratory system, in which venousblood is relieved of carbon dioxide and oxygenated by air drawn throughthe trachea and bronchi into the alveoli. There are two lungs, a rightand a left, the former consisting of three the latter of two, lobes. Thelungs are situated in the thoracic cavity and are enveloped by thepleura.

In humans, each lung is connected with the pharynx through the tracheaand larynx. The base rests on the diaphragm and the apex rises slightlyabove the sternal end of the first rib. The lungs include the lobes,lobules, bronchi, bronchioles, infundibula, and alveoli or air sacs.

The lungs contain about 300 million alveoli and their respiratorysurface is about 70 square meters. Adults average about 15-20respirations per minute. The total capacity of the lung varies fromabout 3.6 to 9.4 liters in adult men and about 2.5 to 6.9 in adultwomen.

The left lung has an indentation, called the cardiac depression, for thenormal placement of the heart. Behind this is the hilum, through whichthe blood vessels, lymphatics, and bronchi enter and leave the lung.

Air travels from the mouth and nasal passage to the pharynx and thetrachea. Two main bronchi, one on each side, extend from the trachea.The main bronchi divide into smaller bronchi, one for each of fivelobes. These further divide into a great number of smaller bronchioles.Additionally, there are about 50 to 80 terminal bronchioles in eachlobe. Each of these divides into two respiratory bronchioles, which inturn divide to form 2 to 11 alveolar ducts. The alveolar sacs andalveoli arise from these ducts. The spaces between the alveolar sacs andalveoli are called atria.

The alveolus is the point at which the blood and inspired air areseparated only by a very thin wall or membrane that allows oxygen andnitrogen to diffuse into the blood and carbon dioxide and other gases topass from the blood into the alveoli. The alveoli contain small poresthat serve to connect adjacent alveoli to each other.

The primary purpose of the lung is to bring air and blood into intimatecontact so that oxygen can be added to the blood and carbon dioxide canbe removed. This is achieved by two pumping systems, one moving a gasand the other a liquid. The blood and air are brought together soclosely that approximately one micrometer (10⁻⁶ meter) of tissueseparates them. The volume of the pulmonary capillary circulation isabout 150 ml, but this is spread out over a surface area ofapproximately 750 sq feet. This capillary surface area surrounds 300million air sacs called alveoli. There blood that is low in oxygen buthigh in carbon dioxide is in contact with the air that is high in oxygenand low in carbon dioxide for less than one second. This allows for theblood to be replenished with oxygen and for the excess carbon dioxide tobe removed.

Hemoglobin, the iron-containing pigment of red blood cells, then carriesthe oxygen from the lungs to the tissues. In the lungs, hemoglobincombines readily with oxygen, by a process called oxygenation, to form aloose, unstable compound called oxyhemoglobin. In the tissues, whereoxygen tension is low and carbon dioxide tension is high, oxyhemoglobinliberates its oxygen in exchange for carbon dioxide. The carbon dioxidethen becomes carried by the blood serum to the lungs, where the wholeoxygenation process begins again.

There have been numerous efforts in the past 40 years to achieveartificial lung function. Unfortunately, no new innovative respiratoryassist therapy has been developed for patients with severe,life-threatening lung disease. This is largely due to inadequateknowledge of pulmonary pathophysiology, a lack of emerging therapies,and insufficient mechanisms for providing intermediate to long-termrespiratory support. The lack of adequate technology for respiratorysupport for the patient with deteriorating lung function, in particular,has had profound effects on the quality of life for this increasinglylarge segment of the population.

The number of deaths annually from all lung disease is estimated to beapproximately 250,000 (150,000 related to acute, potentially reversiblerespiratory failure and 100,000 related to chronic irreversiblerespiratory failure) with an estimated economic burden of disease in therange of 72 billion dollars per year. Furthermore, the emotional toll ofprogressive respiratory failure is profound, particularly as it affectschildren and adolescents with progressive pulmonary disease. The impactof this public health problem can be conceived in terms of the directcosts for intensive, sub-acute, and long-term health care services, andthe indirect costs associated with lost wages and productivity for thepatient and the patient's family, and the increased need for supportservices.

While the death rates for cardiovascular disease, cancer, and all othermajor diseases have recently decreased significantly, the rate of deathrelated to chronic pulmonary lung disease (CPLD) has increased by 54%.Lung disease also represents one of the leading causes of infantmortality, accounting for 48% of all deaths under the age of one. Forthese patients, respiratory assistance during pulmonary failure has beenachieved by employing ventilator therapy, despite the enormous cost andmorbidity associated with this modality.

Furthermore, it is well accepted that closed, positive-pressure,mechanical ventilation, applied at moderate levels of intensity, forshort periods of time, is a somewhat safe and efficient means forimproving gas exchange in patients with acute respiratory failure.However, with prolonged duration of intensive respiratory support,serious adverse effects may occur. These effects, including oxygentoxicity, baromtrauma, altered hormone and enzyme systems, and impairednutrition, may result in further injury to the failing lungs, or addsignificantly to the morbidity and mortality for these patients. As aresult, alternative methods have been sought for augmenting blood gasexchange, where mechanical ventilation is inadequate or cannot be safelyapplied.

In view of the above and other reasons, there has been great interest indeveloping an artificial means for accomplishing physiological gasexchange directly to the circulating blood and bypassing the diseasedlungs. While previous efforts have provided some measure of success,they have been limited in their usefulness or hindered by excessivecost.

One approach to artificial lung function has been by gas sparging ordiffusion of gas across the membrane surface of hollow fibers placedwithin the blood supply. Previous efforts have achieved some success,and have taught much to pulmonary physiologists, but gas sparging ordiffusion has yet achieved the degree of gas exchanges optimallydesired.

Furthermore, other methods and artificial lung systems have beendeveloped from introducing gaseous oxygen by air sparging. However, gassparging is very detrimental to biological tissues such as red bloodcells. Also, gas sparging attempts to control the differential pressureacross thin gas/liquid membranes such as those found in porous-walledhollow fibers.

Another approach to artificial lung function, extracorporeal membraneoxygenation (ECMO), constitutes a mechanism for prolonged pulmonarybypass, which has been developed and optimized over several decades buthas limited clinical utility today as a state-of-the-art artificiallung. The ECMO system includes an extra-corporeal pump and membranesystem that performs a gas transfer across membranes. Despite thenumerous advances in the implementation of ECMO over the years, its coretechnology is unchanged and continues to face important limitations. Thelimitations of ECMO include the requirement for a large and complexblood pump and oxygenator system; the necessity for a surgical procedurefor cannulation; the need for systemic anticoagulation; a high rate ofcomplications, including bleeding and infection; protein adsorption andplatelet adhesion on the surface of oxygenator membranes; laborintensive implementation; and exceedingly high cost. As a result ofthese limitations, ECMO has become limited in its utility to selectcases of neonatal respiratory failure, where reversibility is consideredto be highly likely.

The development of the intravenous membrane oxygenation (IVOX) alsorepresented a natural extension in the artificial lung art, since it wascapable of performing intracorporeal gas exchange across an array ofhollow fiber membranes situated within the inferior vena cava but didnot require any form of blood pump. The insertion of the IVOXeffectively introduced a large amount of gas transfer surface area (upto 6000 cm²) without alteration of systemic hemodynamics. Unfortunately,as with ECMO, the IVOX system has numerous limitations, including only amoderate rate of achievable gas exchange; difficulty in devicedeployment; a relatively high rate of adverse events; and a significantrate of device malfunctions, including blood-to-gas leaks due to brokenhollow fibers.

A further approach to treat lung disease, is through the use of lungtransplants. The improvement of methods to transplant viable lungs intopatients is fundamentally the most significant recent advance in thetherapy of chronic lung diseases. The most common indications for lungtransplantation are emphysema, pulmonary fibrosis, cystic fibrosis, andpulmonary hypertension. Selection conditions emphasize the presence ofirreversible disease localized to the respiratory system, and social andpsychological conditions supportive of the ability to go throughextended pulmonary rehabilitations. In contrast, the absence of theseconditions present relative contraindications to this approach. Thedonor organ should originate in a relatively healthy, infection freeindividual, under the age of 65. Following these guidelines, success hasbeen achieved in increasing numbers for patients throughout the UnitedStates.

Profound limitations in the number of donor organs has made this optionunrealistic for the great majority of patients who would benefit themost. While rationing is the standard for all transplantable organs, theneed for rationing is particularly acute in the case of the lungs, owingto the following issues: (1) the large discrepancy between donor andrecipient numbers (3350 registration for lung transplant in 1999 andonly 862 performed); (2) the relatively low yield of usable lungs, withonly 5-10% of multiorgan donors yielding lungs acceptable fortransplantation; and (3) the absence of effective temporary methods tosupport blood gas exchange during the waiting period prior totransplantation. The complexity of this problem is increased evenfurther, when considering the inevitable compromise between supplyingorgans to patients who are the most ill, and who have the most to gain,but for whom outcomes are generally poor, versus relatively healthierpatients with no complications, who have less need but for whom outcomesare predictably better. For example, a patient with emphysema is highlylikely to achieve a positive outcome from transplantation, but generallywill not exhibit improved survival. In contrast, a patient with cysticfibrosis has considerably higher risk of surgery due to the presence ofmultiorgan involvement of the disease, but for these young patients,successful transplantation optimizes survival.

Therefore, a serious need exists for new technology and therapeuticapproaches that have the potential to provide intermediate to long-termrespiratory support for patients suffering from severe pulmonaryfailure. Also, the need for an efficient and inexpensive technology toachieve sustained gas exchange in the blood, thereby bypassing thediseased lungs without resorting to chronic ventilation, remainsparamount.

SUMMARY OF THE INVENTION

In one aspect, the present invention is directed to an photolyticartificial lung. It may be utilized for lung replacement and/or foroxygenation supplementation of the blood stream. It is particularlyuseful for treating a number of lung afflictions.

The photolytic artificial lung is a device, internal or external to thebody, that utilizes light, such as a laser or lamp, to achievephysiological and therapeutic gas exchange in the blood stream. In suchan exchange, oxygen is dissolved into the blood stream while carbondioxide is removed and pH is controlled. This is due to the use ofphotochemistry. The photolytic artificial lung oxygenates blood withoutthe deleterious effect on red blood cells associated with direct gassparing (i.e. blood cell lysis, pH balance difficulties, etc.), whilesimultaneously controlling blood pH and carbon dioxide content.

More particularly, the photolytic artificial lung includes aphoto-electro chemical cell (or “photolytic cell”) that, in part,operates similar to the photosynthesis process that takes place in greenplants. The photolytic artificial lung utilizes the photolytic cell toconvert light energy in order to simultaneously generate oxygen fromwater, useful acidity and electrical energy. The photolytic cell alsoremoves carbon dioxide from the blood stream. One or more photolyticcells can be included in the photolytic artificial lung of the presentinvention depending on the quantity, quality, etc. of desired gasexchange.

The light energy utilized in the present invention is ultraviolet (“UV”)light or visible light, with the laser form being the most preferred.However, the light energy can also be broad-band, received by the way ofa “light pipe” fiber optic cable or by the way of an attenuated totalreflectance (ATR) link.

In the artificial lung, oxygen is generated from water present in theblood stream by means of the light dependent chemical reactions,photolysis and disproportionation. This is followed by the removal orclearing of carbon dioxide by the reactions of bicarbonate ionprotonation and dehydration.

Photolysis is the initiation of a chemical reaction as a result ofabsorbing one or more quanta of radiation. Here, water is converted intooxygen by a light-activated catalyst, such as a semiconducting metaloxide. The metal oxide is utilized as a photo-absorbent material or aphoto-absorption element. It is photolytically irradiated to form, fromwater present in the blood stream, hydrogen ions, hydrogen peroxide orother forms of oxygen gas precursor (active oxygen, “AO”) and electronsby the absorption of one or more quantra of electromagnetic radiation.The free electrons generated are then electrically conducted away toavoid reversal of the reaction and optionally utilized to driveelectrical devices, such as a pump.

For example, it has been found that active oxygen is readily generatedin the present invention by the use of the anatase form of titania(TiO_(2(a))) as the light absorbent material. The photo energy of light,such as ultraviolet laser light (about 350 nm), selectively excites TiO₂semiconductor transition (about 350-390 nm band, or about 3.1 eV) withminimal material radiation or transmission. The ultraviolet energyproduces charge separation in the anatase form of TiO₂, which thenproduces active oxygen (OA) and free electrons. The free electrons arethen subsequently electrically conducted away due to the semi-conductingproperty of the anatase. Alternatively, other suitable light absorbentmaterials can also be utilized in the present invention at variouswavelengths provided that the energy is sufficient to produce activeoxygen.

Disproportionation is a chemical reaction in which a single compoundserves as both oxidizing and reducing agent and is thereby convertedinto a more oxidized and a more reduced derivative. For example,hydrogen peroxide (active oxygen) produced during photolysis can beconverted by means of manganese dioxide (MgO₂), or other catalyticagents and/or processes, into dissolved oxygen (DO) and water. Thisreaction produces dissolved oxygen (DO) from water and by-passes theharmful gaseous state.

Additionally, in the artificial lung of the present invention, carbondioxide is removed from the blood stream by the means of the reactionsof protonation and dehydration. In essence, the hydrogen ions formedduring photolysis react with the bicarbonate (HCO₃ ⁻) and carbonate (CO₃⁼) ions present in the blood stream causing conversion of these ionsinto carbonic acid. In the presence of carbonic anhydrase, a bloodcomponent, the carbonic acid then quickly dissociates into water andcarbon dioxide. The carbon dioxide gas is then subsequently vented intothe environment.

Alternatively, due to concerns with infection in human lung assistanceapplications, a novel method and device is also disclosed herein forremoving carbon dioxide from the system by molecular absorption. In thisembodiment, carbon dioxide is removed from the blood stream by means ofa carbon dioxide absorber device (i.e., a sorber), or other similargaseous removal devices, under sterile conditions.

Consequently, the artificial lung of the present invention producesoxygen directly from water present in the blood stream, omitting thegaseous state which has previously caused pressure, shear, weight, andbulkiness problems with other blood oxygenation technologies. At thesame time, the artificial lung also utilizes the hydrogen ions producedfrom the water to release the carbon dioxide. Additionally, thereactions occurring in the artificial lung do not involve the generationor use of high temperatures or pressures associated with previousdevices and/or processes. The photolytic artificial lung is preferablydesigned to be self-contained and self-regulated. It requires noexternal gas supply.

A brief description of the pertinent reactions involved in theembodiment of the present invention utilizing anatase as the lightabsorbent material is provided below:

Photolysis:

Disproportionation:

Protonation (H⁺ Ions from Photolysis Reaction):H+Na⁺+HCO⁻ ₃⇄Na+H₂CO₃

CO₂ Gas Generation:H₂CO₃⇄H₂O+CO₂⇑

Catalyzed Dehydration (Optional):

The primary function of the photolytic artificial lung of the presentinvention is to provide respiration assistance in patients with lungdisease, both in acute as well as chronic conditions. However, othermedical applications are also feasible which also require thephotochemical reactions of the present invention and/or the convenienceof photolytic power. These include, among others, in-body drug levelmaintenance and release, and the contribution to the function of otherorgans such as the kidneys and the liver.

Additionally, the mix of products generated by the photolytic artificiallung of the invention, can be used in driving complex chemicalprocesses, such as fermentations, and the regulation of drug levels. Itcan also be used to provide point-of-use chemicals such as hydrogenperoxide. The ability to produce electrical power can further beutilized in remote locations, and in powering small pumps (for example,it is contemplated that the electricity generated from the artificiallung can be used to drive an intravenously located blood pump, etc.).Parallel processes like oxidation and reduction can also be drivensimultaneously at low then high (or visa versa) pH. The presence offundamental oxygen and pH transformations can still further lead to manybroad applications from sensors to industrial chemical processing, andas an energy source to remote sites.

In a more particular embodiment, the photolytic artificial lung of thepresent invention comprises an inlet for receiving blood from the bloodstream of a patient. A pump extracts blood from the patient and movesthe blood into at least one flow-through photolytic cell via the inlet.The photolytic cell contains a light-activated catalyst that convertswater into oxygen, while at the same time removing carbon dioxide asdescribed above. A light supply provides light energy to the photolyticcell. An outlet moves blood out of the photolytic artificial lung andback into a patient.

The photolytic cell is compatible with blood and provides high yields ofoxygen to the blood stream. The resulting photolytic artificial lung iscapable of use externally or internally by a patient, as well as in astationary or portable form. Furthermore, the artificial lung isscalable to allow the photo-activated gas exchanges to be accomplishedin a small and wearable extra-corporeal device, or in an intra-corporealdevice inserted into a patient's venous blood supply.

In a further aspect, the present invention is also directed to aphotolytic cell. The photolytic cell includes a transparent window. Ananode is adjacent to the transparent window. A light-activated catalystabuts the anode. A cell flow through area is adjacent to the lightactivated catalyst. A cation exchange membrane borders the cell flowthrough area. A catholyte abuts the cation exchange membrane. A cathodeis present adjacent to the catholyte and is connected to the anode.

In another aspect, the present invention is further directed to a gasabsorption or sorption device for collecting and converting a gas, suchas carbon dioxide, to a solution or solid. The gas sorption devicecomprises a coalescence compartment including a gas head space and acoelesor connected thereto, wherein gas accumulates and/or isconcentrated in the gas head space. A gas sorber connected to thecoalescence compartment allows for the movement of gas from the gas headspace to the gas sorber and the gas sorber converts gas to a solution ora solid. The sorber can be disposed or regenerated thereby avoiding thecontinuous venting of carbon dioxide to the atmosphere.

In an additional aspect, the present invention is further directed to amethod for delivering oxygen to an aqueous bicarbonate ion solution. Themethod comprises moving the solution into a photolytic cell whereinlight is utilized by a light-activated catalyst to produce oxygen fromwater, with a small concomitant pH change to cause a release of carbondioxide; and moving the oxygenated solution out of the photolytic cell.

In still another aspect, the present invention is yet further directedto a method for oxygenating blood from a patient. The method includesmoving deoxygenated blood into a photolytic cell; converting water todissolved oxygen in the photolytic cell; binding dissolved oxygen toblood hemoglobin; forming carbon dioxide in the photolytic cell;removing carbon dioxide formed in the photolytic cell; and movingoxygenated blood out of the photolytic cell. This process emulates, to acertain degree, selected portions of the natural process by which plantsproduce oxygen, namely photosynthesis, and the way the lung eliminatescarbon dioxide, namely through a pH drop. This method produces dissolvedoxygen directly from water, omitting the gaseous state. It can beutilized to achieve therapeutic gas exchange in patients withrespiratory failure.

These and other objects and features of the invention will be apparentfrom the detailed description set forth below.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will become more fully understood from thedetailed description given below and the accompanying drawings. Thedescription and drawings are given by way of illustration only, and thusdo not limit the present invention.

FIG. 1 shows a perspective view of an embodiment of a photolyticartificial lung designed for external or extra-corporeal usage.

FIGS. 2A-2D illustrate the various embodiments of the photolyticartificial lung set forth in FIG. 1. FIG. 2A shows a generalillustration of the photolytic artificial lung connected externally to apatient. FIG. 2B shows an interior view of the components of oneembodiment of the photolytic artificial lung. FIG. 2C also shows aninside view of an alternative embodiment of the photolytic artificiallung, and FIG. 2D illustrates the chemical reactions occurring therein.

FIG. 3 shows a schematic view of the photolytic cell which was used tocollect the laboratory data set forth herein.

FIG. 4 shows an overall schematic diagram of the preferred embodiment ofthe photolytic artificial lung of the present invention.

FIG. 5 shows a diagram of the gas sorption device.

FIG. 6 shows a schematic diagram of the coalescence collector.

FIG. 7 shows an interior view of the gas sorber device.

FIG. 8 shows a graph illustrating the plot of observed electricalcurrent generated by the photolysis cell versus laser power intensity.

FIG. 9 shows a graph illustrating the relationship of the pH profile ofthe anolyte and catholyte during photolysis using the photolysis cell.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention is directed to a photolytic artificial lung havingamong other components, a photolytic cell. The photolytic cell is thefundamental functional unit of the invention. It acts as a generalpurpose oxygen generation, carbon dioxide remover and a pH controller.The photolytic cell includes a photochemically active material for usein producing various chemical reactions that enable the exchange ofoxygen and carbon dioxide in the blood stream. By optimizing a relativebalance between light activation, photolytic cell surface area and bloodflow, it is designed to maximize efficient gas transfer. The photolyticcell, when used as a photolytic artificial lung application for lungreplacement/supplementation, will oxygenate blood without thedeleterious effect on red blood cells associated with direct gas sparingwhile simultaneously controlling blood pH and carbon dioxide contact.

Moreover, many devices other than an artificial lung can be derived andimplemented based upon the photolytic cell. For example, the photolyticcell can be utilized to perform numerous operations including chemicalprocesses, fermentation systems, regulation of drug levels, andreplacement or assistance of one or more organ functions. Consequently,as a result of the somewhat similar photo-electrochemicaltransformations involved, the photolytic cell component of the inventioncan have additional applications outside of the artificial organ field.

In the preferred embodiment, the present invention is directed to theuse of the photolytic cell in a novel respiratory assist device andprocess i.e., a photolytical artificial lung. The photolytic artificiallung includes one or more photolytic cells having photochemically activematerial and associated components for the production of oxygen, theregulation of pH, the removal of carbon dioxide, and the co-productionof electrical power. The electrical power can be used to produceadditional chemical changes or reactions. Optionally, the invention mayinclude a photolytic chamber to house or hold a sufficient number ofstacked or assembled photolytic cells to perform the rate of gasexchange desired.

The technology of the present invention is based in part, on thephoto-initiated electrochemical transformation that mimics, to somedegree, the natural process of photosynthesis. In photosynthesis, energyderived from sunlight is used to drive key metabolic reactions that fuelthe growth of plants along with the production of oxygen.

The present photolytic artificial lung combines aspects ofphotosynthesis and the operations of the lung. In the lung, oxygen istransferred from the air to the blood as dissolved oxygen that isavailable for binding to hemoglobin (Hb) for transport to body tissues,and carbon dioxide is released from the blood into the air. Theequilibrium shifts from the binding of dissolved oxygen to Hb andrelease of carbon dioxide are driven by gas pressure differences andcarbonic anhydrous catalysis.

In the present invention, the photolytic artificial lung uses lightenergy to produce oxygen from water. Additionally, a concomitant smallpH change causes a release of carbon dioxide from whole blood or serum.In the preferred embodiment, chemical materials formed in the chemicalprocesses from the photolytic artificial lung are insoluble solidsthereby preventing blood contamination.

Preferably, the photolytic artificial lung of the instant inventioncomprises a blood inlet cannula, a pump, at least one photolytic cell, alight source that irradiates the photolytic cells, an oxygenated bloodoutlet cannula and a carbon dioxide vent and/or absorption device. Apower source and/or batteries can be present to power the pump or lightsource. One or more in-line sensors and processors can be present tomonitor and optimize the flow through the system, the amount of oxygenand/or carbon dioxide generation, the presence of toxins, etc.Desaturated blood circulating through the device will be pumped throughthe photolytic cells where light activation will result in oxygengeneration and ultimate carbon dioxide removal.

More particularly, FIG. 1 shows an embodiment of a photolytic artificiallung 10 developed as an extra-corporeal respiratory assist system. Theartificial lung 10 includes a blood inlet 12 that cannulates blood fromthe patient into the artificial lung 10. The blood inlet 12 is connectedto a pump 14 that draws blood from the patient into the artificial lung10. The pump 14 directs desaturated blood through one or more photolyticcells 16 where light activation (for example, laser at 350-380 nm)results in oxygen generation and ultimate carbon dioxide removal via acarbon dioxide sorption device 24 or external ventilation. A powersupply 18 or optional battery 19 activates the light source 20. Thelight source 20 emits light photos 21 which irradiate the photolyticcells 16. In turn, the photolytic cells 16 photochemically initiate aseries of chemical reactions that produce oxygen and remove carbondioxide from the blood. Oxygenated blood travels from the artificiallung 10 back to the patient by way of a blood outlet 22. Consequently,the artificial lung 10 takes blood from the venous circulation of apatient and returns it to the arterial circulation.

The present photolytic artificial lung omits the gaseous state thatcauses problems which have limited other blood oxygenation technologies,while consuming carbon dioxide. It also eliminates the need for anexternal oxygen source and minimizes the risk of inflammation producedby hollow fiber technology.

Also, the present photolytic artificial lung does not require thecareful control of temperature or pressure. As briefly mentioned above,all materials for use in the present photolytic artificial lung remainas insoluble solids to prevent blood contamination. Blood contact withthe coatings is minimized. Diffusion layers, which can decreaseoxygenation rates, are minimized using electrical conduction ofelectrons and cations to and from the photolytic site, as is done inphotosynthesis, by incorporating thin films having good photolytictransparency, and electrical and electrochemical conduction.

The wave length, beam size, pulse duration, frequency and fluency of thelight source are adjusted to produce maximum and/or efficient gasexchange. Similarly, pump rate, flow-through capacity, etc. of thephotolytic cells are also so adjusted. This is accomplished by sensorsand regulators which also monitor reaction chemistry, toxins, etc. Thesensors and regulators have the capacity to auto-regulate variousparameters of the system in response to the conditions monitored by thesensors.

Most preferably, the photolytic artificial lung is designed to provideat least about 150 ml of dissolved oxygen per minute at 5 L/min of bloodflow through the system for a human patient. Also, the componentsutilized for the photoactivated gas exchange are biocompatable.

The photolytic artificial lung can be designed so that it is an extracorporeal device or an intra-corporeal device. For example, thephotolytic artificial lung can be designed as a miniaturized,implantable unit. Such a unit is configured to be implantable and ituses a transcutaneous energy transmission system and/or an internallight source for energy conversion.

FIG. 2A shows a simple representation of a patient attached to aphotolytic artificial lung 10 as an extra-corporal device. FIGS. 2B and2C are enlargement views showing the components of various embodimentsof the photolytic artificial lung 10. FIG. 2D shows the chemicaltransformations which occur in each compartment of the variousembodiments of the artificial lung.

The photolytic artificial lung 10 pumps venous blood from the patient tothe photolytic artificial lung 10 through a blood inlet 12. The venousblood enters by means of a flow distributor 25 into one or morephotolytic cell(s) 16. The photolytic cell(s) may be optionally arrangedto form a stack of photolysis cells 27. The amount of blood entering andleaving the photolytic cell(s) 16 is controlled by flow distributor 25.See FIG. 2B.

A light source 20 irradiates the photolytic cell(s) 16, therebyinitiating the photochemical reactions within the photolytic cell(s) 16that ultimately form dissolved oxygen that binds to blood hemoglobin(Hb). Excess carbon dioxide and hydrogen formed from the chemicalreactions in the photolytic cell(s) 16 enter one or more gas sorptiondevices 24 for storage and/or eventual venting through a venting outlet28. Once the blood has been oxygenated, and the carbon dioxide removed,the blood returns to the artery of a patient by way of blood outlet 22.Among the components of the photolytic artificial lung not illustratedin this embodiment is the blood pump, power supply, control electronicsand sensory technology for monitoring reaction chemistry, the amount ofoxygen, carbon dioxide, etc. generated the presence of potential toxins,etc.

The main component of the photolytic artificial lung is the photolyticcell 16. See, for example, FIG. 2C. Light energy 21 from a light source20 enters the photolytic cell 16 through a transparent window 30 andactivates a layer of light-activated catalyst 32. As discussed in moredetail below, an example of such a light activated catalyst is anatase(TiO₂). Depending on the catalyst 32 used, the light-activated catalyst32 converts water into intermediate active oxygen, hydrogen ions andexcess electrons, or directly converts water into dissolved oxygen. Anoptional second catalyst 34 can be used to convert the intermediateactive oxygen to dissolved oxygen, O₂. An example of such a secondcatalyst is manganese dioxide (MnO₂). Excess electrons are formed duringthe conversion of water to dissolved oxygen and are conducted out fromthe catalyst 32 to an anode conductor layer 36 such as gold or titaniummetal film. In chamber 37, the dissolved oxygen binds to hemoglobin (Hb)in the blood and the oxygenated blood returns to the patient via anarterial blood outlet 22.

Additionally, in chamber 37, bicarbonate ions which are also present inthe deoxygenated blood react with the hydrogen ions generated above toform carbonic acid. The carbonic acid is then converted to water andcarbon dioxide by carbonic anhydrase. The water formed reacts withelectrons at the cathode 38 to form hydrogen gas (H₂) and hydroxylgroups. The hemoglobin also releases carbon dioxide when the oxygenbinds to the hemoglobin. The excess carbon dioxide and hydrogen createdfrom the reactions occurring in the photolytic cell 16 enter one or moregas sorption devices 24 for storage or venting.

FIG. 3 shows a flow-through embodiment of the photolytic cell 16. In theflow-through cell embodiment, the following main components of thephotolytic cell 16 are assembled, i.e. a conductive coating of vacuumdeposited Ti metal 36, a coating of adherent TiO₂ (anatase) 32, anoptional MnO₂ particulate layer 34, and then tested using a bicarbonatesolution. A UV laser light 20 was shown on the transparent glass orquartz substrate so to initiate the reactions. As discussed below, thiscell was utilized to collect pH and data as a function of laser U.V.irradiation demonstrating the effectiveness of the invention.

In this regard, the photolytic cell 16 of FIG. 3 includes a transparentwindow 30 or wave guide for the entry of light energy in the form ofphotons 21 from a light source 20 such as an ultraviolet laser light. Onone side of the glass slide is an anode conductor layer 36, such astitanium metal film. Attached to the anode conductor layer 36, is alayer of a light activated catalyst 32 such as anatase (TiO₂). Anoptional catalyst layer 34, such as manganese dioxide, is adjacent tothe light activated catalyst layer 32. The photolytic cell 16 includesone or more layers of silicone gaskets or spacers 40 and an acrylichousing 42. A pair of anolytes 44 (in/out) are connected to the lightactivated catalyst layer 32 or optional catalyst layer 34 and extendthrough the photolytic cell 16 away from the transparent window 30. Thephotolytic cell 16 further includes a cation exchange member 46, such asa NAFION® membrane. A pair of catholytes 48 (in/out) are connected tothe cation exchange member 46 and extend outwardly through thephotolytic cell 16 generally away from the transparent window 30. Thephotolytic cell 16 further includes a cathode layer 38, such as Pt foil,adjacent to the cation exchange member 46. The operation and use of thisembodiment of the invention is more particularly described in theExamples below.

FIG. 4 is a schematic drawing showing the electrical and chemicaltransformations which occur in the photolytic cell 16 of the photolyticartificial lung 10. Venous blood (low in oxygen and high in carbondioxide) from a patient enters the photolytic cell 16 through inlet 12by way of a peristaltic pump 14. Light photons (hv) 21 generated bylight source 20 enter through a transparent window 30 or waveguide andactivate the light activated catalyst 32 such as 100 μm TiO₂ (anatase).The light activated catalyst 32 either directly converts water todissolved oxygen or converts water to active oxygen and hydrogen ionsand an optional second catalyst 34, such as maganase dioxide (MgO₂) on aporous film, converts active oxygen (e.g. H₂O₂) into dissolved oxygen(DO). The dissolved oxygen then binds to hemoglobin present in theblood.

The electrons released from the conversion of water to oxygen arecollected in the collector electron anode 36. An electrical currentformed from a battery 49 allows the electrons to flow from the anode 36to the cathode 38, such as graphite or nickel, so that the electrons donot react with the active oxygen to cause a back reaction and thereformation of water.

The electrical current and electron flow can be regulated by a currentregulator 50 or resistor 52. The electrons can react with water to formhydrogen gas, H₂, and a hydroxyl ion (OH⁻). The hydrogen gas formed ismoved to a gas sorption device, where it is stored and/or released(i.e., expired). Sodium (Na⁺) ions from the blood migrate across thecation exchange membrane 46 and react with hydroxyl ions to form sodiumhydroxide (NaOH) in the catholyte 48. The hydrogen ions formed from theconversion of water at the light activated catalyst reacts withbicarbonate ions to form carbonic acid, which is converted by carbonicanhydrase enzyme present in the blood or added to form carbon dioxideand water. The carbon dioxide formed in the photolytic cell 16 alongwith the carbon dioxide released from the blood is moved to one or moregas sorption devices 24 or vented. The oxygenated blood exits thephotolytic cell 16 via an outlet 22 and returns to the artery of thepatient.

The various particular components and/or processes of the presentinvention are described in more detail below:

1. Transparent Window 30

The transparent window 30 can be formed from glass, quartz slides,quartz, etc. Glass is useful in forming the transparent window providedthat the UV transparency is adequate at the wavelength needed. Quartzslides are also useful because of its high UV transparency. For thetransparent window, light entry into and through the transparent windowcan be from the back, side, or bottom. Edge illumination through thetransparent window can optionally include a lens or wave guide.

The transparent window can further include a wave guide. A wave guideuniformly distributes photons (hv) from the light over the surface ofthe light activated catalyst. Particularly, the wave guide causes thelight photons to travel in a path so that the photons maximally contactthe entire layer of the light activated catalyst. Light enters the waveguide in the side of the transparent window generally parallel to thesurface of the light activated catalyst that is attached to thetransparent window. The wave guide allows for maximal light photoncontact with the light activated catalyst without directly illuminatingthe side of the entire light activated catalyst attached to thetransparent window. The wave guide also allows form maximal photolyticcell staking because light is not required to directly illuminate thelight activated catalyst but rather can be indirectly illuminated byside or edge entry in the transparent window. The wave guide providesadditional efficiency to light used in the photolytic cell because thelight can be spread across the entire surface of the light activatedcatalyst.

2. Anode Conductor Layer 36

The anode conductor layer 36 conducts electrons formed from the reactionof water to oxygen out of the anode. The anode conductor layer preventsthe electrons from reacting back with the oxygen to reform water,thereby allowing maximal formation of oxygen. The anode conductor layeris applied or attached to at least one side of the transparent window.

The anode conductor layer can be formed at least two different ways. Theanode layer can be formed by attaching a thin film of uniform metallicconductor to the transparent window using vapor deposition. The filmpreferably has a thickness of less than about 0.2 μm. Preferably, thefilm is formed from gold or titanium. Gold remains metallic at allconditions but can be very efficient at UV light blockage or reflection.Titanium can be oxidized to TiO₂ by adding O₂ to the deposition chamberto yield a possible catalyst layer with excellent adhesion.

The anode conductor layer 36 can also be formed by using photo-resisttechnology. Under photo-resist technology, grids are prepared with masksusing vapor deposition. Conductor line spacing, width and thicknessoptimization may be required to prevent excessive attenuation, andprovide sufficiently close conductive areas to sweep electrons away fromthe light activated catalyst layer.

3. Catalysts 32 and 34

A light activated catalyst 32 is coated onto the anode conductor layer.The light activated catalyst is photochemically activated and reactswith water to form dissolved oxygen or a free radical oxygenintermediate that is ultimately converted to dissolved oxygen. The termactive oxygen in the present application defines any free radical oxygenintermediate formed in the photolytically catalyzed reaction of waterthat is ultimately converted to dissolved oxygen. The active oxygenformed is in the form of a peroxide, such as hydrogen peroxide, H₂O₂, orperoxide ion salt, hydroxyl free radical, super oxide ion, etc., and isconverted into dissolved oxygen in the presence of a catalyst. Theactive oxygen formed depends on the light activated catalyst used. Also,depending on the light activated catalyst used, water may bephotolytically converted directly into dissolved oxygen without firstforming an active oxygen.

Several different catalysts can be employed for producing dissolvedoxygen photochemically. One catalyst that can be used to photochemicallyproduce oxygen is zinc oxide. By using zinc oxide, peroxide (H₂O₂) isproduced directly from water at blood pH. H₂O₂ is an excellent form ofactive oxygen for providing sufficient potential diffusion distance, andalso for the disproportionate reaction to dissolved oxygen and water viaa solid MnO₂ catalyst (similar to green plant O₂ generation site)occurring photochemically at <340 nm by way of metal ion assisteddisproportionation with catalase and other hydroperoxidases. Zinc oxidefilm has other positive attributes including, known film formationtechnology (e.g. via the zinc/nitrate/glycine reaction), low toxicityconcerns, and low cost.

An additional catalyst that can be used to photochemically producedissolved oxygen is tungstate (WO₃) that is exposed to visible light andusing e⁻ _(scb) removal. WO₃ yields oxygen (O₂) directly from waterwithout the need to first produce an active oxygen species. Oxygen isgenerated stoichiometrically and the “back reaction” is unfavored sothat there is not significant competition to the direct formation ofdissolved oxygen. Only visible light is needed to generate dissolvedoxygen from WO₃, no more than about 496 nm. WO₃ films present lowtoxicity concerns. Preferably, the use of WO₃ further includes theremoval of excess e⁻ _(scb) formed during oxygen formation from water.

Another catalyst suitable for reacting with water is TiO₂ (anatase)irradiation with, followed by dissolved oxygen production at a metalcatalyst, such as a MnO₂ catalyst, or other similar catalyst. TiO₂removes the e⁻ _(scb) efficiently from the production area in order toultimately obtain good dissolved oxygen production and minimize any backreaction to reform reactants. The removal of e⁻ _(scb) is performedthrough conduction via the semi-conductor property of the TiO_(2(a))with enhancement via application of a small DC bias voltage. TiO₂irradiation also presents low toxicity concerns. TiO₂ provides very highinsolubility and kinetic inertness to minimize dissolution and foulingduring use and maintenance. Preferably, UV light is chopped or pulsedduring TiO₂ irradiation to allow time for the chemical reactions tooccur since with continuous irradiation causes the e⁻ _(scb) toaccumulate and force a back reaction to form water. A pause in theirradiation allows time for the slower, but still extremely fastirradiation in the range of μsec to msec to occur to occur.

A further catalyst for reacting with water to ultimately form dissolvedoxygen is a semiconductor powder (SCP)-filled UV/VIS light transparentthermoplastic film. SCP-filled thermoplastic film is relativelyinexpensive to manufacture and form into shape. SCP film is easilymoldable, extrudable, cut and machined. SCP can be used very efficientlyin surface applied only form. Also, SCP has low toxicity concerns.Optimized commercial products (conductive plastic filler powders) areavailable with good properties for dispersion, particle-to-particleelectrical conductivity (for e⁻ _(scb) removal), and resistance tosloughing off that can be used with the present photolytic artificiallung.

The following additional preferred conditions may be used for each ofthe above-mentioned catalysts. First, an application of a small (e.g. upto a few volts DC) bias voltage can be applied to help ensure that thee⁻ _(sch) is quickly conducted away from the production site. Second, achopped illumination, instead of a continuously applied illumination,may allow secondary chemical reactions to occur since the secondarychemical reactions are slower than the photochemical reactions andenhance photo yields by allowing the excited electrons to exit thesystem and not be present for regeneration of starting material, i.e.,water.

Of the above-mentioned catalysts, the TiO₂ (anatase) catalyst followedby a second metal catalyst is the most preferred. When the TiO₂ catalystis used, the light-titania interaction is the first step in the ultimateformation of dissolved oxygen. It is known that surface hydratedparticulate TiO₂ (anatase) solid, TiO_(2(a))—OH₂ or Ti^(IV)O_(2(a))—OH,is an efficient UV light (hν) acceptor at wave lengths <390 nm,resulting in active oxygen formation from sorbed water and hydroxylgroups. The most probable reaction is believed to be:Ti^(IV)O_(2(a))—OH+hν→Ti^(III)—^(•)OH^(•)

It is noted that other bonds to Ti have been omitted for clarity. Thereactant and product of the above reaction are solid materials. In theabove reaction, H₂O is already bonded to the surface of the TiO_(2(a))catalyst as H₂O or as hydroxyl ion (OH⁻), i.e. Ti^(IV)O_(2(a))—OH₂ orTi^(IV)O_(2(a))—OH, respectfully. Hence, no atoms are required to moveduring the very fast photon absorption process. The * represents a lowlying excited electronic state where the energy of the photon is used totransition or excite an electron from a nonbonding orbital on the oxygento a molecular orbital centered on the titanium ion, hence convertingthe titanium into a trivalent oxidation state. The molecular orbitalcentered on the titanium ion is known to be a part of the semiconductionband (“scb”), and so the electron is readily conducted away from thesite to form a bipolar charged grain, or, if connected to a closed DCelectrical circuit, resulting in full charge separation, i.e.,Ti^(III)—^(•)OH^(•)→[Ti^(IV)—^(•)OH]⁺ +e ⁻ _((scb)⇑)

If the e⁻ _(scb) is not conducted away or otherwise removed by reactionwith an oxidant present in the solution, the e⁻ _(scb) could react withthe hydroxyl free radical and reverse or back react so that the systemwould return to its original state and form water. In this latter casethere would be no net reaction and the photolytic energy will appear asa small amount of heat. Hence the charge separation process and removalof e⁻ _(scb) is considered an important first step of the photolyticcell dissolved oxygen generation process.

The hydroxyl free radical (^(•)OH) group present is used to representthe initial form of the active oxygen generated by the photolyticprocess. It is not certain that •OH is the dominant species present whenTiO_(2(a)) is photolyzed. The active oxygen formed could generally be inthe form of a superoxide, hydrogen peroxide, or a hydroxyl free radical.However, the form of this active oxygen produced has sufficientthermodynamic driving force to form active oxygen from water. For theTiO_(2(a)) catalyst at neutral pH, these highly reactive hydroxyl freeradicals either back react as described above, or rapidly dimerize toform (μ-peroxo) titanium (IV) and hydrogen ions, i.e.

These H⁺ ions are valuable for blood-CO₂ level control. The rate ofdissolved oxygen production is the rate at which the active oxygensplits out to form O_(2(aq)) and reforms TiO_(2(a)), i.e.Ti^(IV)—O—O—Ti^(IV)→Ti^(IV)—O—Ti^(IV)+½O_(2(aq)) (as dissolved oxygen)

In an unwanted but unharmful second side reaction, any O_(2(aq))produced can react with e⁻ _(scb) previously produced but not yetconducted away. These e⁻ _(scb) negative charges tend to reside on thesurfaces of the TiO₂ particles so that the negative charge are mostseparated. Therefore, these e⁻ _(scb) electrons are available forreduction reactions with O₂ or the μ-peroxide linkage to produce speciessuch as O₂ ⁻, O⁼, O⁻, etc., thereby decreasing dissolved oxygen yields.In order to minimize side reaction, the illumination is pulsed insteadof continuous. The delay caused by illumination pulsation allows the e⁻_(scb) to be conducted away in one direction and the dissolved oxygen todiffuse away in another (E. Pelizzetti, M. Barbeni, E. Pramauro, W.Erbs, E. Borgarello, M. A. Jamieson, and N. Serpone, Quimica Nova(Brazil), 288 (1985)). Also, illumination pulsation prevents the localpopulations of O_(2(aq)) and e⁻ _(scb) from becoming so high thatreaction between them becomes fast. The pulse rates involved areextremely short in the μsec-msec range so that there is little effect onO_(2(aq)) production rates. Enhanced yields are also possible forphotolytically established charge separation when a bias voltage ispresent across the coating. (X. Z. Li, H. L. Liu, and P. T. Yue,Envison-Sci-Technology, 2000, 34, 4401-4406.) A small bias voltage mayalso be used to further reduce the amount of e⁻ _(scb) present andproduce more dissolved oxygen.

Another way to increase the amount of dissolved oxygen production in theTiO_(2(a)) system is to provide a means to speed the rate of release ofthe trapped μ-peroxide as hydrogen peroxide as to active oxygen.Ti^(IV)—O—O—Ti^(IV)+H₂O→Ti^(IV)—O—Ti^(IV)+H₂O_(2(aq))

H₂O₂ is an excellent form for the active oxygen species as it readilymigrates and is easily catalyzed to disproportionate into dissolvedoxygen and water. catalyst

Stable free radicals (SFRs) can be used to release the trappedμ-peroxide as hydrogen peroxide. SFRs can exist as free radicals forextended periods of time relative to the hydroxyl free radical. SFRshave been found useful for promoting electron transfer reactions. Theyelectronically and reversibly rearrange into reduced or oxidized speciesone electron at a time as set by the reaction conditions. Biologicalsystems are known to use SFRs as respiratory carriers, such as quinonecoenzymes including ubiquinone, vitamin K, etc. The SFR shuttles thereactivity from the point of generation to the point of H₂O₂ production,or even directly to the metal ion MnO₂ catalyst for dissolved oxygenproduction. Components found in biological systems such as vitamins E,C, K, etc. also may function in the role of SFRs except without recycle.At least four classes of SFRs exist from which a suitable agent can beselected: hindered hydroxylated aromatics (quinones, substitutedphenolics); organic peroxide precursors (alcohols, etc.); peracidprecursors (acylating agents, etc.); and nitroxides, RN→O.

Therefore, for the TiO_(2(a)) photocatalyst to be useful, a means forreleasing the μ-peroxide energy is needed, such as soluble H₂O₂, sinceH₂O₂ can diffuse to the MnO₂ for dissolved oxygen production, or byconducting the oxidizing power to another active oxygen form, such asSFRs in the adjacent solution that can be used in dissolved oxygenproduction, or using the Ti^(IV)—O—O—Ti^(IV) content to electronicallyremove electrons from the MnO₂ cluster/particle (as is done in greenplant photosynthesis by the “D” protein). In the last means, only anelectron flows from the water through the MnO₂ to the μ-peroxo linkagethrough delocalized bonds. This electron replaces the e⁻ lost from theTiO_(2(a))—OH system as e⁻ _(scb).

The formation of H₂O₂ as the active oxygen is valuable since H₂O₂ can berapidly converted to dissolved oxygen in 100% yield using many differentmethods: thermally; metal ion catalysis; particulate/surface catalysis;base catalysis; and free radical reaction with reductant initiation.Preferably, metal ion catalysis, such as, MnO_(2(s)), provides anefficient catalyst for H₂O₂ disproportionation to water and O₂, on thinfilm substrate constructs.

Photo catalyst systems such as zinc oxide, ZnO, release peroxide as theactive oxygen more readily than does TiO₂. Less acidic metal ions underthe Lewis acid/base theory definition cannot sufficiently stabilize thehighly alkaline peroxide ion relative to water protonation (pK_(a1) ofH₂O₂ is 11.38 (25° C.)) to form it within the solid phase, and sohydrogen peroxide, H₂O₂, is readily formed from ZnO:

ZnO films and particles can be prepared in a number of ways with varyingbut controlled composition, morphology and porosity. For example,mirrors of zinc, doped zinc, and zinc alloys and can be sputtered downonto an optically transparent support, followed by oxidation withO_(2(g)). This treatment produces a metal/metal oxide (Zn/ZnO) film.Another highly effective approach to semiconducting ZnO-based films isto utilize a process for optical glass coatings. (L. R. Pederson, L. A.Chick, and G. J. Exarhos, U.S. Pat. No. 4,880,772 (1989).) The opticalglass coating technique is based on applying a zinc nitrate/glycineaqueous solution as a dip or spray, followed by drying (110° C. for 15min), then heating (450-500° C. for 3 min) to initiate a self-oxidationreaction during which the carbon and nitrogen exits as gases leaving anadherent yet porous film bonded to the underlying surface (e.g. glass)and is referred to as the glycine nitrate process. (L. R. Pederson, L.A. Chick, and G. J. Exarhos, U.S. Pat. No. 4,880,772 (1989).) The ZnOfilm is normally produced doped with alumina by including aluminumnitrate in the aqueous formulation for the initial dip. Many other metalion blends are also possible with this technique.

Tungstate only requires visible light to produce dissolved oxygen, andproduces dissolved oxygen directly without requiring a second catalystto form dissolved oxygen. The lower photon energy requirement for WO₃ isdue to the smaller band gap of 2.5 eV versus at least 3 eV forTiO_(2(a)). As with the TiO₂ anatase system, high yields are possiblewith the WO₃ catalyst if the e⁻ _(scb) is removed. The production of O₂increases very significantly if RuO₂ (ruthenium oxide) is placed on thesurface of the WO₃. This is consistent with the fact that RuO₂ is aknown good catalyst for O₂ production and so represents a route toimproving other approaches.

An advantage may exist if the dissolved oxygen producing film could be afilled plastic. Such materials are often inexpensive and manufacturedeasily. Commercial sources exist for semi-conducting, low lightabsorbing, inorganic fillers for plastics which are supplied in readymade condition for incorporation into plastics, making the plasticselectrically conductive. For example, E.I. duPont Nemours, Inc. sellselectroconductive powders (EPC) under the trade name ZELEC® ECP for suchpurposes. The conductive substance in ZELEC® ECP is antimony-doped tinoxide (SnO₂:Sb). The bulk of these materials, onto which the conductoris coated, are familiar inorganics such as mica flakes, TiO₂, and hollowsilica shells, or ECP-M, ECP-T and ECP-S respectively. PureSnO₂:Sb-based material is designated ECP-XC and is a much smallerparticle than the other materials. About 25-45% by weight of the ECPproducts are used so that the particles are sufficiently close to eachother to provide internal electrical connections throughout theotherwise non-conducting plastic. ECP-S and ECP-M normally perform bestfor lower concentrations. Thin films of ECP-XC can provide an attractivecoating because they are very fine grained and strongly light absorbing.

The TiO₂ layer can be formed a variety of ways. The TiO₂ layer can beformed by sol gel, drying and baking. A product under the trademarkLIQUICOAT® from Merck & Co., Inc., which hydrolyzes Ti(OR)₄ typematerial in water to form TiO₂ and 4ROH can be used to form the TiO₂layer under a sol gel/drying/baking process. TiO₂ can also be formedfrom preparing an anatase suspension from dry powder, then dipping,drying, and baking the suspension to form the TiO₂ layer. Another waythe TiO₂ layer can be formed is by e-beam evaporating titanium andsubsequently exposing the titanium to O₂ within a deposition chamber.The TiO₂ layer can also be formed by adding titanium salt to water andadjusting the pH to ˜2-7 to form a suspension, then dipping thesuspension and allowing the suspension to dry.

Active oxygen is created from TiO₂ by irradiation with UV light, but thechemical form of the active oxygen is very reactive and can be lost byside reaction occurring in close proximity to the TiO₂ particle surfacewhere active oxygen is generated. There are at least three ways tominimize the loss of active oxygen to unwanted side reaction: 1) movethe active oxygen to dissolved oxygen conversion point closer to theactive oxygen generation point, i.e. move the metal ion catalyst asclose as possible to the TiO₂, which may require intimate contactbetween these two materials, in the order of angstroms; 2) electricallyconnect the two points, as is done in photosynthesis by a proteincapable of conducting electrons; or 3) convert the active oxygen into alonger lived intermediate active oxygen species that has time to migrateto more distant MnO₂ centers for conversion to dissolved oxygen.

The amount of active oxygen lost by side reactions can be minimized byintroducing an active oxygen carrier molecule into the media, or “D,” byanalogy to a photosynthetic system. Agents for use with species D can beselected from two groups, those that readily form organic peroxides, andthose that form “stable” (i.e. long-lived) free radicals. Organicperoxides are useful because they easily produce dissolved oxygen whencontacting MnO₂, and readily form by oxygen insertion. The organicperoxide reactions are as follows:[TiO₂]—Ti^(IV)—OH+hv→{[TiO₂]—Ti^(III•)OH}where the excited electronic state corresponds to the ligand-to-metalcharge transfer (free radical pair), and is followed by the reaction:{[TiO₂]—Ti^(III•)OH}+H₂O→[TiO₂]—Ti^(IV)—OH—H+⁺+^(•)OHwhere conduction of the e− into the semiconductor conduction band andaway from the side of the particle near the ^(•)OH preventsrecombination of that e⁻. As shown in the reaction above, the TiO₂anatase is regenerated. The above reaction produces a hydrogen ion foreventual CO₂ removal. Also, the active oxygen produced in the abovereaction is in close proximity to TiO₂ as a free radical hydroxylgroups, ^(•)OH.

As ^(•)OH is extremely reactive, lasts only for a very short time anddoes not diffuse far. One way to increase the amount of time that ^(•)OHis present is by introducing a species that stabilizes the ^(•)OH.Similar to photosynthesis, a species “D” is introduced into the testsystem to capture the hydroxyl free radical in a longer lived species.The species D is generally shown the in following chemical reaction:D+^(•)OH→D^(•)where D can be RC(O)OH:

or D can be a free radical scavenger that forms a stable free radical:

or D can be 2,6-di-tertbutyl phenol:t-Bu-Ar—OH+^(•)OH→t-Bu-Ar—O^(•)+H2O

The 2,6-di-tertbutyl phenol is the most desired D species, as a stronglyreducing ^(•)H radical is not formed that would consume OH⁻ and[TiO₂]—Ti^(III) in wasteful reactions, regenerate the startingmaterials, and result in a low photochemical yield.

The catalyst used to convert active oxygen into dissolved oxygenincludes metal ions capable of redox cycling, such as Fe^(II), Fe^(III),Cu^(I), Cu^(II), Co^(II), Co^(III), Mn^(II), Mn^(III), Mn^(IV), etc., ormetal oxides formed from metal ions capable of redox cycling, such asmanganese dioxide, MnO₂. The present reaction produces dissolved oxygendirectly from water and by-passes the gaseous state. The MnO₂ catalystis most preferred because it forms dissolved oxygen efficiently and isnot highly selective of the active oxygen form.

One way to facilitate the conversion of active oxygen to O₂ is by dopingthe surface of the TiO₂ anatase with manganese (Mn). Surface doping theTiO₂ with Mn provides a highly productive active oxygen to O₂ conversioncatalyst. Active oxygen disproportionation is rapid when dropped on aMn-doped anatase. Alternatively, active oxygen can also be converted toO₂ by placing MnO₂ on the surface of the anatase in conductive form. Inthis form, electrons are catalytically passed from water to the activeoxygen region of the anatase. Such an arrangement more closely mimicsphotosynthesis O₂ production.

Another way to convert active oxygen to O₂ in the photolytic cell is byusing a MnO₂ octahedral molecular sieve (MOMS) material as the dissolvedoxygen catalyst. The MOMS material has an open gel-like structure and isclosely related to zeolites in structure. The MOMS material is easilyformed from manganese salts through precipitation and drying.

Active oxygen may also be converted to O₂ in the photolytic cell by asuperoxide dismutase (SOD) catalyst. SOD catalyst is already availablein the human body and can provide the required conversion of activeoxygen, e.g. as O₂ ⁻. into a dissolved oxygen precursor, i.e. H₂O₂, tosupplement the photolytic cell and Mn-doped anatase.

Blood is routinely exposed to active oxygen forms and blood already hasbuilt-in measures for self protection against low levels of excessiveactive oxygen. (“Inorganic Biochemistry”, G. L. Eichhorn (Ed)., Chap.28, p 988 (Elsevier, Scientific Publ., NY (1975), and “Advances inInorganic and Bioinorganic Mechanisms”, A. G. Skes (Ed), p 128 (1986)(Academy Press, NY)) Active oxygen forms within the body in the form ofspecies such as peroxides (R—O—O—H) and superoxide (O₂ ⁻ _((aq))), whichare disproportionated to dissolved oxygen and H₂O respectively byhydroperoxidases, such as catalase which contains zinc ion, peroxidasewhich contains iron ion, etc., and superoxide dismutase metal ion-basedenzymes, such as ferriprotophyrin IX. Alternatively, these enzymes canutilize active oxygen forms to oxidize a wide range of chemicalreductants such as ascorbic acid and other vitamins such as such asvitamin E and vitamin K. Although the photolytic artificial lung doesnot rely on such protection mechanisms, it is noteworthy that low levelsof such molecules are not new to body chemistry and that conventionalmechanisms for handling such exposures exists.

4. Blood Exchange

Hemoglobin from blood follows the following steps of reactions withinthe photolytic cell.

-   Hb(h.s. Fe^(II))+O₂→Hb(I.s Fe^(II))O₂-   HbO₂+2H⁺ (pH 6.8-7.6)→H₂Hb2⁺+O₂-   N— of two alpha-chains (pKa˜8.0) and His β146-   (pKa˜6.5) residues are bases for H⁺ reaction

When water reacts with a light activated catalyst, the hydrogen ion thatis released rapidly reacts with an HCO₃ ⁻ ion and forms H₂CO₃. Thephotolytic cell has excess HCO₃ ⁻ ions to react with hydrogen ions.

The photolytic cell allows the blood to achieve the proper mass balance.The mass balance of blood traveling through the photolytic cell is asfollows:

Alternatively, quinone can be replaced with Fe(CN)₆ ³⁻. The quinone orFe(CN)₆ ³⁻Q could be in homogeneous solution or film form.

5. Cation Exchange Membrane 46

The cation exchange membrane 46 allows for the diffusion of cations inthe photolytic cell. Particularly, the cation exchange membrane allows acation, such as a sodium ion (Na⁺) from blood to diffuse through themembrane and subsequently form sodium hydroxide (NaOH) in the catholyte.The cation exchange membrane is commercially available under thetrademark NAFION® and is available from E.I. du Pont Nemoirs inc.NAFION® cation exchange membranes are a perfluorosulfonic acid/PTFEcopolymer in an acidic form. Although NAFION® cation exchange membranesare the preferred membrane, one skilled in the art would recognize thatother cation exchange membranes are also suitable in the photolyticcell. Anode

The anodic compartment of the photolytic cell has the following seriesof reactions:

The overall net anodic reaction from the above reactions is as follows:hν+¼Hb+2NaHCO₃→2CO_(2(g))⇑+H₂O+½Hb_(0.5)O₂+2e ⁻+2Na⁺

The two electrons formed in the anodic reaction are conducted away tothe cathode via the anode conductor layer. The two Na⁺ ions are moved toa catholyte via a cation exchange membrane.

6. Catholyte 48

Sodium hydroxide (NaOH) builds in the catholyte during the series ofreactions in the photolytic cell. It is preferred that the NaOH ispurged occasionally from the catholyte. If sodium chloride (NaCl) isused in the catholyte instead of NaOH, NaCl(s) may eventually formwithin the catholyte and would periodically be purged.

The reactions occurring in the cathode of the photolytic cell are asfollows:

The overall net cathodic reaction is as follows:2e ⁻+2Na⁺+2NaHCO₃→H_(2(g))⇑+2Na₂CO₃

The Na₂CO₃ that is produced causes pH to rise. Based upon the overallanodic and cathodic cell reactions, the overall net photolytic cellreaction is:hν+¼Hb+4NaHCO₃→H_(2(g))+2Na₂CO₃+2CO_(2(g))+H₂O+½Hb_(0.5)O7. Battery/Current Regulator

As shown in FIG. 4, the photolytic cell can include a battery 49,current regulator 50, or resistor 52. An electrical current formed froma battery 49 allows electrons to flow from the anode 36 to the cathode38. The initial bias voltage caused by the current supplied from thebattery initiates the removal of electrons formed during the conversionof water to dissolved oxygen and prevents the electrons from reactingwith the active or dissolved oxygen to reform water. The initial biasvoltage also allows more dissolved oxygen to be produced as the removalof the electrons minimizes the reformation of water. Additional externalelectrical contacts can monitor or apply a particular voltage to thephotolytic cell.

The current regulator and resistor help control the flow of electronsfrom the anode to cathode, thereby controlling the amount of dissolvedoxygen formation. The resistor creates a fixed control in the currentflow, whereas the current regulator can be adjusted to increase ordecrease the resistance of the current flow. Increasing the resistanceof the current lowers the number of electrons flowing from the anode tothe cathode, thereby lowering the overall production of dissolvedoxygen. Decreasing the resistance of the current increases the flow ofelectrons from the anode to the cathode, thereby increasing the amountof dissolved oxygen produced.

8. Optimal Gas Sorption Device 24

Continual venting of carbon dioxide gas out of the photolytic cellpresents the problem of potential infection. A gas sorption deviceminimizes and provides control over potential infection risks byavoiding continuous venting of the CO₂ to the atmosphere. The gassorption device captures CO₂ gas released from the oxygenated blood in aconcentrated form. The concentrate can be processed or disposed ofoccasionally so that the sterility of the photolytic cell is notcontinuously subjected to possible contaminants due to the continualventing of the CO₂ gas.

CO₂ can be captured using a number of different ways by a gas sorptiondevice 24. The gas sorption device can use the process ofchemi-absorption and convert CO₂ into a concentrated solid or solutionform. The concentrate formed in the gas sorption device can then bedisposed of as disposable cartridges having liquid or solid CO₂, orregenerated.

FIG. 5 shows the general schematic of the gas sorption device 24 andpath of CO₂ to the gas sorption device 24 for absorbing CO₂. Thephotolytic cell 16 forms dissolved oxygen that associates with thedeoxygenated blood flowing through the cell. The CO₂ produced in theanode of the photolytic cell 16 from the conversion of bicarbonate ionto carbonic acid is present as small bubbles as a result of carbonicanhydrase activity. These bubbles are readily released within acoalescence compartment 54 so that the use of membranes are avoided.Four moles of CO₂ gas is released per mole of O₂ gas formed. When O₂ isformed at the targeted flow of 150 cc/min gas at STP, the moist CO₂ flowrate is about 600 mL/min at STP. CO₂ is trapped when entering thecoalescence compartment 54 by a gas coelesor 56. In or near the bottomof the gas coalesor 56 an entry point 58 exists for hydrogen gas (H₂)coming from the cathodic compartment. The H₂ gas merely sweeps acrossthe head space 60 above the gas coelesor 56 in the coalescencecompartment 54 and collects CO₂ gas. The flow is provided by the samepump 14 that is used to provide the photolytic cell 16 with blood sincethe photolytic cell 16 is either a fully liquid-filled closed system, ora cascading overflow (but non-portable) system. The CO₂/H₂ gas mixtureexits the top of the gas head space 60, near the blood entry point. WhenO₂ is formed at the targeted flow of 150 cc/min gas at STP, the H₂ flowrate is at least about twice the O₂ flow rate or 300 mL/min (STP). Thegas mixture then flows to a sorber 62.

FIG. 6 shows a coalescence compartment 54. The coalescence compartment54 can be a small plastic reservoir having a relatively small volume,and can be any shape. Preferably, the coalescence container 54 has adownward tilt. The whole blood travels through the coalescence container54 through the coelesor 56 and returns to the patient at the bottom ofthe tilt. H₂ gas enters at an entry point 58 into the gas head space 60and sweeps the CO₂ through the gas head space 60 and into a sorber (notshown). The coalescence container 54 can be used as a temperaturecontrol point.

FIG. 7 shows a sorber 62. The sorber 62 converts CO₂ gas into either asolution or solid depending on the sorbent 64 used within the sorber 62without the need for mechanical mixing or pumping. The high capacity,low pressure drop, sorber 62 for CO₂ gas operates at mild pressure witha gravity feed and without the need for high surface area contactor. TheCO₂/H₂ gas mix enters the sorber 62 at an entry point 66 near the bottomof the sorber 62. Intimate mixing of gas and liquid is accomplished bythe 900 flow path changes, cross-path gas/liquid paths, andcounter-current configuration. The CO₂ reacts with the sorbent 64 in thesorber 62 to form a solid or solution. The solid or solution formed canbe removed through an outlet 70. Hydrogen gas can be swept out through asweeping outlet 68 and be reused in the coalescence compartment (notshown). Preferably, the sorber 62 is small and has a total internalvolume of about 25 cc. The entire sorber 62 is contained within thesterile unit. Since blood is not involved in the sorber 62, potentiallydetrimental effects in the blood are avoided. Also, the large orificesand membrane-free operation prevents potential fouling. The sorber 62can have a vertical orientation but can also be designed with broadorientation accommodation. The entire sorber 62 is contained within thesterile unit.

The sorbent material 64 within the sorber 62 can be a solid or asolution. As a solution, the sorber can also be the catholyte for thephotolytic cell. The sorbent 64 as a solution is consumed at a rate of2-6 mL/min for the a CO₂ gas flow rate of 600 mL/min at STP. The highcapacity, low pressure drop, sorber 62 for CO₂ gas operates at mildpressure with a gravity feed and without the need for high surface areacontacter. Alternatively, the sorber 62 can use a solid sorbent 64 wherethe sorbent 64 is a packed bed of sorbent granules. Since blood is notinvolved in the sorber 62, potentially detrimental effects in the bloodare avoided. Also, the large orifices and membrane-free operationprevents potential fouling. The sorber 62 can have a verticalorientation but can also be designed with a broad orientationaccommodation. Sorbent materials are selected to. react with the CO₂ gasto form bicarbonates and carbonates as solutions, solids, orcombinations of these. Individual sorbents can be blended to obtainsynergistic blends which, for example, might react faster, be more costeffective, and/or hold more carbon dioxide equivalents than the purematerials. Table 1 is a list of sorbent materials along with their CO₂capacity equivalents.

TABLE 1 Sorbent Solutions and Solids for CO₂ Maximum molarity CO₂Solution solution % sorbent in when fully loaded Chemical or densitysolution (20– or of sorbent CO₂ sorbing Form of Sorbent Solid g/cc 25°C.) initially charged. capacity Sorbed CO₂ Na₂CO₃ soln 2.53 31.3 (35°C.) NaHCO₃ NaOH soln 1.52 50 19.01 NaHCO₃ catholyte and (w/OH- fromNa₂CO₃ PAL cell) NaCl soln TBD TBD TBD TBD NaHCO₃ catholyte and (w/OH-from Na₂CO₃ PAL cell) KCl soln TBD TBD TBD TBD KHCO₃ and catholyte K₂CO₃(w/OH- from PAL cell) KOH soln TBD TBD TBD TBD KHCO₃ and catholyte K₂CO₃(w/OH- from PAL cell) CaCl₂ soln 40. 5.03 5.33 cc/mi CaCO₃(s) catholyte320 cc/hr pKsp = 8.32 (W/OH- from 7.7 L/hr PAL cell) Ca(OH)₂ solid TBDTBD TBD TBD CaCO₃(s) pKsp = 8.32 MgCl₂ soln 1.28 30.00 4.021 catholytew/OH- from PAL cell) Mg(OH)₂ solid TBD TBD TBD TBD MgCO₃(s) pKsp = 9.2soda lime solid TBD TBD TBD TBD CaCO₃(s) pKsp = 8.32 nonvolatile solnTBD TBD TBD TBD R₄N⁺HCO₃ ⁻ amines (e.g. MEA, DEA, etc.) (1) MEA and DEAare monoethanol amine and diethanol amine respectively. Polyol amines,polyamines, and zwitterionic materials are other suitable organic CO₂sorbents. (2) CaCO₃ is not expected to be regeneratable. (3) Note thatthe halide salt systems, e.g. NaCl, KCl, CaCl₂ and MgCl₂, or mixturesthereof as are represented by brines such as Lockes-Ringer solution,saline solution, etc., sorb CO₂ by using the cathodically produced OH⁻,the salt just providing charge balance at the membrane and electrode,and in the sorber/desorber.

HCO₃ ⁻ loses CO₂ easily and the sorbent can be regenerated thermally,disposed of as a disposable cartridge, or regenerated continuouslythrough the self sterilizing and self-cleaning caustic heating operationat mild temperatures and pressures. Alternatively, the sorbent can becontinuously regenerated. For the carbonate sorbent system, the pH willvary from an initial pH of 11.6 to a pH of 8.3 when exhausted and couldbe monitored using a pH indicator dye or pH electrode.

Hydrogen gas produced in the cathode and used to sweep the CO₂ from theblood to the coalescence compartment will accumulate unless vented. H₂,being an extremely small molecule, readily diffuses through mostnon-metallic materials, especially plastics, ceramics, etc. The ventingof H₂ can be controlled by selecting materials of construction thatallow diffusion. No particular membranes, vessels, pumps, filters, oneway valves, etc. are required to diffuse H₂. The role of H₂ as a sweepgas has a very broad range of acceptable flow rates for proper functionsince the CO₂ will self-flow in its absence and a negative pressure willdevelop in the CO₂ sorber as the chemistry is quantitative (CO₂efficiently absorbed down to low P_(CO2) values).

8. Light Supply 20

The light supply is used in the photolytic cell to provide the photonenergy necessary to activate the catalyst converting water into oxygen.The light source can be from any known light source including, but notlimited to, sunlight, UV light, laser light, incandescent light, etc.,depending on the activation requirement for the light activated catalystused. Preferably, the blood flowing through the photolytic artificiallung is not exposed to the light in order to prevent irradiation of theblood.

The light source may provide a particular wavelength of light dependingupon the catalyst used. When tungstate (WO₃) is used as a lightactivated catalyst, the light source exposes visible light in order toactivate WO₃. When TiO₂ or ZnO is used as a light activated catalyst,the light source used has a wavelength in the UV range.

Preferably, the light source used in the photolytic artificial lung is alaser light. The wavelength of laser light can be manipulated in orderto attain a higher efficiency in exciting the light activated catalystand forming active oxygen. Also, laser light allows the photolyticartificial lung to dissipate less overall heat. The laser light can bedirected in a small area to energize the light activated catalyst andavoid contact or irradiation with other components of the photolyticartificial lung. A particularly preferred laser light that can be usedto activate TiO₂ is an argon laser at 364 nm (400 mwatts/cm²), which hasa total power of about 2 watts, although other UV sources, including anHG arc lamp at 365 nm line, are also available.

It is preferred that the light from the light source be evenly spreadwithin the photolytic cell. The even spreading of the light from thelight source allows for maximal excitation of the catalyst in order toconvert more water into either active oxygen or dissolved oxygen. Alongthese lines, light from the light source can enter the photolytic cellthrough the transparent window from many positions. Light from the lightsource can enter directly through the transparent window and come intocontact with the catalyst. Alternatively, light can enter thetransparent window from a side, back, bottom, or corner position andmove through the transparent window by a wave guide to provide photonenergy and excite the light activated catalyst. Side entry of light intothe transparent window of the photolytic cell occurs at about at least a68° angle. Preferably, side entry of light into the transparent windowoccurs at an angle of from about 70° to about 80°.

9. Pump

A peristaltic pump or some other simple pump drives blood through thephotolytic artificial lung. The pump draws venous deoxygenated bloodfrom a patient and moves the blood through the photolytic artificiallung. Preferably, the photolytic artificial lung only requires a pump todraw blood from a patient, as the flow produced by the pump drawingblood from the patient also moves the blood through the photolytic cellfor oxygenation and back into the patient.

10. Sensors Monitoring Reaction Chemistry

The photolytic artificial lung can include one or more sensors thatmonitor the different chemical reactions occurring within the photolyticcell. The sensors can be used to measure for potential toxins and toxinlevels. Various sensors and sensor systems can be used including visualobservations of color changes of redox indicator dyes or gas bubbleformation, closed electrical current measurements and pH measurements,and dissolved oxygen probe analysis. Gas chromatography assays can alsobe performed. A dissolved oxygen probe can be used to test and monitorO₂ generation, as dissolved oxygen, in real time. Also, the photolyticartificial lung can incorporate one or more portals to insert adissolved oxygen probe, CO₂ probe, pH monitor, etc. in differentlocations if necessary. The photolytic artificial lung can alsoincorporate separate sampling chambers to trap gas bubbles for testing.These sampling chambers could also incorporate a device, such as aseptum for a hypodermic needle for instance, to obtain a sample forfurther testing. One skilled in the art would recognize numerous sensorscould be used for monitoring the reaction chemistries occurring withinthe photolytic cell.

The photolytic artificial lung and photolytic cell can also include oneor more process regulator devices that respond to the readings providedby the sensors. The process regulator devices increase or decrease theamount of dissolved oxygen or CO₂ output, lower toxin levels, etc.,depending on the requirements of the patient or of the photolytic cell.It is within the purview of one utilizing the photolytic artificial lungto determine what process regulator devices are required.

All of the seals in the photolytic artificial lung are made of an inertmaterial that properly seals blood flowing through the photolyticartificial lung from accidental contamination. The seals of thephotolytic lung should also be formed of a material that does notinteract with the blood. Preferably, the seals are formed of asilicone-based material.

Laminar flow is minimized within the photolytic artificial lung.Minimization of laminar flow is accomplished by using current commercialcells, such as electrodialysis, electrodeionization, etc. Commerciallyavailable cells accommodate electrodes, membranes, and thin liquidchambers with flow distributors, and provide good seals and corrosionresistance. The cells are available in lab scale units for processdevelopment work. A particularly preferred commercial cell is theFM01-LC device from ICI Chemicals and Polymers, ElectrochemicalTechnology, Cheshire, UK.

Multiple Photolytic Cells

Preferably, the photolytic artificial lung uses a plurality ofphotolytic cells in a stacked formation. The plurality of photolyticcells receive blood flow from the venous circulation and are exposed tophoto-activation via a directed laser light source. The stacking of aplurality of photolytic cells allows for a large overall surface areafor blood to receive maximal exposure to dissolved oxygen. Also,stacking a plurality of photolytic cells allows the overall photolyticartificial lung to achieve a smaller size, thereby allowing thephotolytic artificial lung to be miniturized.

Photolytic Cell has Broader Applications

The photolytic cell as described may be used for photochemical processesbeyond the preferred embodiments described above. The photolytic cellmay be used in other organs to cause or regulate chemical reactionsoccurring within the system. The photolytic cell may be used in organsincluding, but not limited to, heart, lungs, brain, kidney, liver, etc.Alternatively, the photolytic cell may be used outside of a biologicalsystem in order to control reactive activity. Also, one having ordinaryskill in the art would recognize that the photolytic cell could also beused as a potential energy source due to the production of electrons.

EXAMPLES

Having generally described the invention, the following examples areincluded for purposes of illustration so that the invention may be morereadily understood and are in no way intended to limit the scope of theinvention unless otherwise specifically indicated.

A prototype photolytic artificial lung was produced in order todemonstrate the ability of the device and accompanying processes tore-oxygenate synthetic blood serum (Locke's Ringer Solution), withconcomitant CO₂ removal and pH control, using thin film constructs. Inthis regard, a photolytic test flow cell (see FIG. 3) was constructedusing exemplar materials for the elements of the photolytic artificiallung—a conductive coating of vacuum deposited Ti metal, a coating ofadherent TiO₂ (anatase), a MnO₂ particulate layer, and then abicarbonate solution. A U.V. laser light was introduced to thetransparent glass or quartz substrate. This cell was used to collect pHand cell electrical current data as a function of laser U.V.irradiation. The details of the construction of such a prototype and theresults produced thereby are discussed below.

In this regard, a photolytic test flow cell as shown in FIG. 3 of thephotolytic artificial lung was prepared. Specifically, among othercomponents the following layers of the photolytic cell were assembled:light source 20; transparent window 30; e⁻conductor (anode) 36; TiO₂photo catalyst 32; MnO₂ catalyst 34; NAFION® cation exchange membrane46; catholyte 48; and conductor (cathode) 38. The particular parametersof these components and others are as follows:

Glass/Quartz Slide 30 Preparation

A glass slide was degreased by swirling in toluene or MEK. The slide wasflash dried in air for less than about 1 minute. The slide was thensoaked in warm Micro® cleaning solution for about 2 minutes. The slidewas rinsed thoroughly with 18MΩ DI water. The slide was immediatelythereafter soaked in a water bath for about 2 minutes. The slide wasrinsed thoroughly with water from a squirt bottle and drained but notallowed to dry. With caution, the slide was submerged in a solution ofconcentrated sulfuric acid and was allowed to stand for 2 minutes. Aplastic hemostat was used to hold the slide when it isinserted/withdrawn from the sulfuric acid. The slide was withdrawn,allowed to drain, and rinsed thoroughly with water. The slide was thensoaked in a water bath for about 2 minutes. A water break test was thenperformed on the slide. Using a plastic (Nalgene®) beaker with coverwatch glass, the slide was dipped for 2 minutes in a solution of 0.1% HFand 1N HCl. The surface of the glass now contained Si—OH linking groups.These slides were kept wet, and stored in 5% HNO₃.

Catalyst Layer 32 Preparation

About 1.0 g of TiO₂ (anatase) was added to a plastic (Nalgene®) beakerwith a cover watch glass, and a magnetic stir bar. In a hood, 80 mL of0.1% HF and 1N HCl was added to the TiO₂. A stirrer stirred the beakeruntil the solids were well suspended. The beaker was mixed for 60seconds and was proceeded immediately to the next step of dividing theslurry between two 50 mL capped centrifuge tubes. The tubes werecentrifuged for at least 5-10 minutes. The supernatant was discarded.Each tube was rinsed 3 times with 40 mL portions of water. The tube wascapped, vortexed thoroughly, centrifuged, decanted, and the steps wererepeated. Each tube was rinsed 3 times with 40 mL portions ofisopropanol (iPrOH). Optionally, one or more inorganic silane and/ortitanate-coupling agents can be added to the last alcohol rinse tofacilitate agglomeration and adhesion in the final coating. Theaggressive oxidizing environment of the UV/TiO₂ during use may rapidlydegrade organic-based coupling agents and so inorganic couplings may befavored.

Application of the Catalyst to the Glass Slide

The pretreated TiO₂ anatase particles were magnetically re-suspendedfrom one of the tubes in a jar containing isopropanol sufficiently deepto cover the glass microscope slide. Magnetic stirring was initiated tokeep the particles suspended. The amount of particles used is anadjustable parameter in determining the thickness of the final coatingproduced.

A sufficient amount of Ti(iOPr)₄ (TTIP) was added to yield a 0.2 vol %solution (e.g., by adding 160 uL TTIP per 80.0 mL isopropanol). Using aplastic hemostat to hold the slide, the treated glass slide was rinsedthoroughly with water and was again tested under the water break test.The slide surface was rinsed thoroughly with isopropanol. The slide wassoaked for 2 minutes in isopropanol and rinsed again with isopropanol.The slide was immediately hung in the TTIP/isopropanol solution andstirred. The vessel was covered to minimize pickup of moisture from theair, and allowed to react for about 120 seconds. During this time, theTTIP reacted with the Si—OH groups on the surface of the glass slide toform O—Si—O—Ti-iOPr linkages, although the linkages may not have formedrapidly until the heating step below. The slide was removed very slowly(e.g. 1 cm/min) using the hemostat and was laid flat on an invertedbottle cap in a vacuum desiccator to dry for a few minutes. The standingtime in the room air (humidity level and contact time) was adjustablesince water vapor diffuses to the surface of the slide causinghydrolysis reactions (the “sol” in sol-gel), i.e.,Ti(iOPr)₄+2H₂O→TiO(iOPr)₂+2 iPrOHTiO(iOPr)₂+2H₂O→TiO₂+2 iPrOH

Excess water must be avoided so that the silanol groups on the surfaceof the slide may react, i.e.,glass surface-Si—OH+Ti(iOPr)₄→Si—O—Ti (iOPr)₃ +iPrOH

Similar reactions couple the TiO₂ anatase particles to the surface ofthe glass and to each other,TiO₂(anatase)−Ti—OH+Ti(iOPr)₄→TiO₂(anatase)−Ti—O—Ti (iOPr)₃ +iPrOH

It is noted, however, that thoroughly desiccated (water-free) surfacesare also not useful since dehydration of surface Si—OH and Ti—OH groupsoccurs, which would remove the hydrogen needed to produce the iPrOHproduct at low energy. The time spent at this room temperature conditioncan be adjusted since the coating slowly reacts during this time.

While still lying flat, the slide is oven-dried at 80-90° C. for 20minutes to finish the cure. The time, temperature and heating rate (°C./min) parameters are adjustable. Heating too fast can blow outsolvent, causing massive disruption of the film due to out gassing,while heating too high a temperature can cause too much condensationresulting in shrinkage, leading to pulling away of the film andcracking. Porosity is expected to be important so that water canpenetrate and active oxygen can leave the reaction zone.

In order to obtain slides having a thicker TiO₂ coating, the above stepsare repeated one or more times.

The slide was heated to 250° C. for two hours to fully cure and set thecoatings. This temperature was needed to convert the amorphous TiO₂formed from the TTIP into anatase. Ind. Eng. Chem. Res. 1999 38(9),3381. Alternatively, a slide can be pretreated as above except heat thecoating to 350° C. at the rate of 3° C./min and hold at this temperaturefor 2 hr. Miller, et al. Environ. Sci. Technol. 1999, 33, 2070. Anotheralternative is to prepare the sol-gel solution in place of theanatase/TTIP slurry. Colloid C in Aguado, M. A., et al., Solar EnergyMaterials. Sol. Cells, 1993, 28, 345. The slide was then removed andallowed to cool to room temperature.

The coating adhesion of the TiO₂ anatase to the glass slide was testedby abrasion with a rubber policeman, tape test, etc. Also, the coatingadhesion was tested for other properties including thickness, tendencyto crumble/flake off, visual appearance, etc.

The experiments were repeated as needed to improve adhesion and otherproperties. An additional step of a 400° C. treatment for one hour canused to set TiO₂ (anatase) particles onto a quartz sand slide(Haarstrick, et.al. 1996).

TiO₂ Coating Photochemistry Testing

Two TiO₂ coating photochemistry testing procedures were conducted, thefirst to determine whether electrons were generated and the second todetermine whether active oxygen was generated. First, the TiO₂ wastested by a negative charge/electron generation test. Methyl viologen(MV²⁺) blue color (MV⁺) was applied onto the anatase coating and wassubjected to laser light. A rapid appearance of dark blue colorqualitatively, validating electron formation. MV⁺ blue color was notpermanent since MV⁺ is a free radical/charge transfer complex, whicheasily releases e⁻ and returns to colorless ground state. Dried coatinginhibited the performance of coating (dried minerals block surfacesites), but was easily cleaned.

A second test conducted on the TiO₂ coating layer was the active oxygengeneration test. Methylene blue was used on the TiO₂ coating todetermine the presence of active oxygen. The methylene blue color wasrapidly destroyed at the point of the laser light in the presence ofanatase coating, validating active oxygen formation, since oxidizedoxygen reacts with methylene blue.

Light Source

The light source used was an argon laser at 364 nm line (400 mwatts/cm²)available (tunable to lower powers). The argon laser used has a totalpower of 2 watts. Alternatively, a number of UV sources were availablefor use, including Hg arc lamps using a 365 nm line.

Anode Conductor Layer 36

The anode conductor layer was formed by placing a very thin film ofuniform metallic conductor having a thickness of less than about 0.2 μmusing e-beam vapor deposition onto a transparent window. The thin filmwas formed of Ti metal. Conductor line spacing, width and thicknessoptimization may be required for the anode conductor layer to preventexcessive attenuation while provide sufficiently close conductive areasto sweep electrons away from TiO₂ layer.

Dissolved Oxygen Generating Catalyst Layer 34

A dissolved oxygen generating catalyst layer was formed from MnO₂particles onto the surface of the TiO₂ (anatase) layer. The MnO₂particles were applied (<5 u) as a iPrOH slurry with or without theanatase/Ti(iPrO)4 mixture. A significant surface of the TiO₂ (anatase)layer was coated (˜⅓) by the MnO₂. Adding the MnO₂ drop wise andallowing it to evaporate was effective. The MnO₂ was added to increase %surface area covered by MnO₂ particles and to make the MnO₂ moreadherent using the Ti(iOPr)₄ binder.

Flow Through Cell

The flow through cell was designed with fluid inlets and outlets on thesame side. Silicone gaskets and spacers, acrylic external housing andstainless steal tubing connectors were used in forming the flow throughcell. In the flow through cell, the anode was the continuous Ti plateand the cathode was a platinum foil strip.

Electrical Connection of Flow Through Cell

The electrical connection of the flow through cell was wired as an opencircuit with a current meter and current regulator inline. Theelectrical connection of the flow through cell could also be formed byapplying bias voltage added with the in-line current meter and currentregulator. The electrical connection of the flow through cell could alsobe formed by placing a resistor and a current meter inline with avoltage reading across the resistor.

Divided Cell

A divided cell was designed with both sets of fluid inlets and outletson the same side with the through-anode, through-acrylic housing andsilicone spacer internal flow paths and on the side opposite the glassslide. The divided cell was further designed to include silicone gasketsor spacers, acrylic external housing, NAFION® membrane, and stainlesssteel tubing connectors.

Active Oxygen Testing

A Locke's Ringer saline test solution was prepared with 150 ppm redoxdye (methyl viologen, MV²⁺). Also, a 10 uM solution of methylene bluewas prepared in the Locke's Ringer solution. Matthews, R. W., J. Chem.Soc., Faraday Trans. 1, 1989 85(6), 1291. The molar absorbtivity formethylene blue at 660 nm is 66,700±350 cm⁻¹M¹. The coated test slide wasassembled with an attached UV lamp/laser. The Locke's Ringer solutionwas then added to the coated test slide via a circulating pump. Aftersteady conditions were attained, the coating was illuminateddirectly/indirectly with UV light. The saline solution was monitored forappearance of blue color (MV²⁺(colorless)+e−→MV⁺(blue)) and dissolvedoxygen. Gas samples were sampled for GC assay (CO₂, O₂ not due to air).

Results

The artificial lung was tested in order to determine whether thechemical formulations occurred as predicted. The testing was conductedusing Locke's Ringer solution, which is a saline solution that mimicsblood. The qualitative results of the testing are as follows:

1. Highly efficient U.V. light absorption by thin films of TiO₂(anatase) to impart energy into the anatase matrix was visually apparentin that the UV light is substantially absorbed. Attenuation by any metalconducting film present was measured and corrected separately.

2. Generation of active oxygen (AO) at the anatase surface using theenergy from the UV light was evidenced by methylene blue dyedisappearance at the surface of the anatase film opposite the sideirradiated by the UV laser.

3. Generation of free electrons (e⁻) at the anatase surface using theenergy from the UV light was evidenced by methyl viologen blue dye colorappearance at the surface of the anatase on the side opposite the sideirradiated and only at the location of irradiation.

4. Transport of the free electrons (e⁻) generated above to a conductiveTi anode surface, which were then swept away so that the free electronsdo not recombine with the active oxygen also produced above wasevidenced by electrical current in the anatase semiconductor film, to ametallic collector, wire and amp meter. The electrical current was foundto flow only when the laser was on and the electrical current neverflowed when the laser was off. The effect was observed through numerousoff/on cycles, and the electrical current measured was proportional tothe laser intensity up to a saturation point.

5. The release of hydrogen ions (H⁺) and pH drop was found for theanodic compartment in a continuously circulated and irradiated cell. Theopposite pH change was found for the cathodic compartment, which wasconsistent with the pH effect expected when water is separated intoactive oxygen and hydrogen ions at the anatase surface. FIG. 9 shows aplot of the pH profile of the anolyte and catholyte during photolysisusing the photolytic cell. The opposite trends in the plot are aspredicted based on the photosynthesis mimic chemistry, decrease in pH inthe anolyte and a pH increase in the catholyte. The lower initial pH inthe catholyte in Run 1/6 reflects a startup condition with a slightlylower pH. Run 1/7 used a pre-equilibrated photolytic cell to remove anyinconsistent readings during start up conditions.

6. The conversion of HCO₃ ⁻ ions from the synthetic serum electrolyte,i.e., Locke's Ringer solution, into CO₂, was in part observed by theformation of more H₂O. H₂O is the expected product to be formed alongwith CO₂ during the bicarbonate ion conversion to carbonic acid andultimate conversion to H₂O and CO₂ using the H⁺ ions released during theformation of active oxygen. CO₂ production was measured by gaschromatography (GC) analysis of off-gases, or calculated from pHchanges. The CO₂ level found by GC analysis was significantly greaterthan atmospheric level, further indicating the formation of CO₂.

7. The generation of alkalinity at the cathode and related pH changeindicated that the free electrons produced during the reaction of waterinto active oxygen were conducted away from the anode and consumed in anon-O₂ reducing manner, i.e., by reduction of water to hydroxide ion andH₂ gas.

8. Generation of O₂ as dissolved oxygen from an MnO₂ catalyst coating onthe anatase from an active form of oxygen added to the test media wasfound.

All of the verified steps appeared to react at good rates. Using theelectrical current generated, a rough size for the photolytic cell unitfor a 100 ml/min O₂ flow rate was calculated and found reasonable. Also,a number of coating fabrications were tested that were designed to allowMnO₂ particles, as a coating or dopant, to react with long-lived,soluble forms of active oxygen. These MnO₂ coatings were found togenerate abundant quantities of dissolved oxygen under the testingconditions.

Calculating Size of Photolytic Cell Required

Preliminary testing was conducted on the photolytic cell to determinethe size of a cell required to generate the target oxygen rate in anaverage adult human body of about 150 mL/min (STP) of O₂ for 5 L/min ofblood flow, which is the average normal adult human blood flow rate.FIG. 8 shows the measure of the cell current versus the laser powersetting in 0.60 g/L NaHCO₃ and 4% MeOH electrolyte. It is noted that thelaser power setting is not the same as the actual impinging laser beamenergy, but rather the laser power setting is greater than andproportional to the actual laser beam energy by a factor of about 2.Also, the power setting is of the laser itself and not of the 363.8 nmbeam after it is separated from the other two lines produced by thelaser. The laser power setting was measured after the laser moved aroundthe optics bench and penetrated the glass slide and Ti collector film

Although the data in FIG. 8 represents early exploratory testing and isfar from optimized, it was used to calculate the size of a cell thatwould be needed to generate the target oxygen rate, 150 mL (STP)/min.From FIG. 8, a limiting cell current density of 70 uA/cm² can beestimated. Using this value, a cell surface area needed to generate 150cc O₂ gas/min (STP) was calculated. If one flat sheet cell were used incontact with the blood, it would need to be 7.5×7.5 meters in area (56m²) to provide 150 mL O₂ gas/min. Since no optimization has been done todate which might improve rates and since stacking of smaller plates toachieve a net large surface area is routine in electrochemical celltechnology, this level of performance is considered encouraging as anearly test result. Although the quantum efficiency was not determined inthis qualitative testing, it appeared to be low. Many options areavailable to improve on the quantum yield. An improvement of 10 timeswould require a blood contact area (BCA) of 75 cm on a side, which thencould be cut in half (by area) to 53 cm square by double siding thecell, i.e., one cathode, two anodes. Using six pairs, as is done inautomotive batteries for example, reduces these dimensions to a cube ofabout 20 cm on a side, well within acceptable dimensions for anemergency use extracorpreal device without ancillary equipment.Therefore, a sufficiently small photolytic artificial having a smallstack of photolytic cells appears possible with a 10 time improvementover the current production rates, assuming a high correlation betweencell electrical current and Is dissolved oxygen production. Reasonabletarget values for optimized photo current efficiencies are expected tobe in the 0.1-10% range.

FIG. 8 also shows that spreading the laser beam to about 1 cm² resultedin about the same current production as did leaving the beam as a 3-4 mmspot. This result suggests that the photons were being supplied fasterthan they could be consumed. Therefore, significantly enhancedutilization of the laser power appears possible. Efficiency enhancementsmight be accomplished by pulsing the beam to allow the chemicalreactions to keep up and/or further spreading it using optics.

The invention has been described with reference to the preferredembodiments. Obviously, modifications and alterations will occur toothers upon a reading and understanding the preceding detaileddescription. Particularly, it is clear to one having ordinary skill inthe art that the photolytic cell can be modified and used in numerousother reactions and reaction systems. It is also apparent that thepresent photolytic cell can be used in organs other than the lungs, andthat the cell can be used in living systems other than humans.Furthermore, one skilled in the art would appreciate based upon thepreceding detailed description that the photolytic cell can be used informing chemical reactions in solutions other than whole blood. It isintended that the invention be construed as including all suchmodifications and alterations in so far as they come within the scope ofthe appended claims or the equivalents thereof.

1. A method for delivering oxygen to blood comprising: providing theblood into a photolytic cell; converting water present in the blood intodissolved oxygen by a light-activated catalyst in said photolytic cell,wherein the dissolved oxygen is formed directly from water and bypassesthe gaseous state; binding said dissolved oxygen to an oxygen carrier insaid blood; and removing said blood out of said photolytic cell.
 2. Themethod of claim 1, further comprising removing carbon dioxide from saidblood in said photolytic cell.
 3. A method for delivering oxygen to ablood comprising: providing the blood into a photolytic cell; convertingwater present in the blood into dissolved oxygen by a light-activatedcatalyst in said photolytic cell, wherein the dissolved oxygen is formeddirectly from water and bypasses the gaseous state; producing carbondioxide from said blood in said photolytic cell; removing said carbondioxide from said blood; binding said dissolved oxygen to said blood;and removing said blood out of said photolytic cell.
 4. A method foroxygenating blood from a patient comprising the steps of: providingblood from a patient into a photolytic cell; converting water present inthe blood into dissolved oxygen in said photolytic cell by a series ofphotochemical reactions; binding the dissolved oxygen to bloodhemoglobin; forming carbon dioxide in said photolytic cell; removingcarbon dioxide formed in said photolytic cell and blood; and removingoxygenated blood out of said photolytic cell and returning the blood tothe patient.
 5. A method for producing oxygen and removing carbondioxide from a patient's blood comprising the steps of: providingdeoxygenated blood received from a patient into a photolytic cell,wherein said photolytic cell contains a light activated catalyst havingthe ability of converting water to oxygen upon light activation;providing light to said photolytic cell and activating said catalystwherein water present in the blood is converted into dissolved oxygenand carbon dioxide is formed in said photolytic cell; binding thedissolved oxygen to blood hemoglobin in said photolytic cell; removingthe carbon dioxide formed in said photolytic cell; and removing theoxygenated blood out of said photolytic cell and returning the blood tothe patient.
 6. The method of claim 1, wherein the oxygen carrier ishemoglobin.
 7. A method for oxygenating blood from a patient comprisingthe steps of: contacting blood from a patient with a photolytic cell;converting water present in the blood into dissolved oxygen; and bindingthe dissolved oxygen to blood hemoglobin; and removing oxygenated bloodout of said photolytic cell and returning the blood to the patient.
 8. Amethod for oxygenating blood from a patient comprising the steps of:providing blood from a patient into a photolytic cell; converting waterpresent in the blood into dissolved oxygen in said photolytic cell by aseries of photochemical reactions; converting bicarbonate ions presentin the blood into carbonic acid in said photolytic cell; allowing thedissolved oxygen to bind to hemoglobin located to red blood cells;allowing the carbonic acid to form carbon dioxide in the photolyticcell; removing oxygenated blood from the photolytic cell; removingcarbon dioxide in the oxygenated blood; and returning the oxygenatedblood to the patient.
 9. The method of claim 4, wherein the bloodprovided into the photolytic cell is venous blood.
 10. The method ofclaim 4, further comprising converting bicarbonate ions present in theblood into carbonic acid in the photolytic cell.
 11. The method of claim10, wherein further comprising converting the carbonic acid to carbondioxide.
 12. The method of claim 4, wherein further comprising producingcarbon dioxide when the dissolved oxygen is bound to the solution.